Rabinovitch, Rachel

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin lymphoma provide expert, multidisciplinary recommendations for the diagnosis and treatment of Hodgkin lymphoma. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Hodgkin Lymphoma focuses on the management of newly diagnosed and relapsed/refractory classic Hodgkin lymphoma in adults aged 18 to 60 years.

The treatment landscape of B-cell lymphomas has significantly evolved in recent years with approval of novel targeted therapies. CD3 × CD20 bispecific antibodies and CD19-directed monoclonal antibodies and antibody–drug conjugates have demonstrated efficacy in relapsed/refractory follicular lymphoma (FL). Bruton tyrosine kinase (BTK) inhibitor–based regimens are emerging as effective treatment options for patients with TP53-mutated classical mantle cell lymphoma (MCL). Results from ongoing clinical trials suggest that the addition of CD3 × CD20 bispecific antibodies to chemoimmunotherapy improves outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). These NCCN Guideline Insights highlight significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, MCL, and DLBCL.

Abstract Background NRG Oncology NSABP B-39/RTOG 0413 compared whole-breast irradiation (WBI) to accelerated partial-breast irradiation (APBI). APBI was not equivalent to WBI in local tumor control. Secondary outcome was quality of life (QOL). Methods The QOL sub-study used validated self-report questionnaires, including the Breast Cancer Treatment Outcome Scale (BCTOS) and the 36-Item Short Form Health Survey (SF-36) vitality scale. Assessments occurred before random assignment, at treatment completion (chemotherapy or radiotherapy), 4 weeks later, at 6, 12, 24, and 36 months. Primary aims: cosmesis change equivalency (baseline to 3 years; a priori margin of equivalence 0.4 standard deviations) and fatigue change superiority (baseline to end of treatment [EOT]) for APBI vs WBI, by patient groups treated with or without chemotherapy when appropriate. Results From March 21, 2005 to May 25, 2009, 975 patients enrolled in this sub-study; 950 had follow-up data. APBI had 3-year cosmesis equivalent to WBI (95% CI = -0.0001 to -0.16; equivalence margin -0.22 to -0.22) in all patients. The APBI group without chemotherapy had less EOT fatigue (P = .011; mean score APBI 63 vs WBI 59); the APBI group receiving chemotherapy had worse EOT fatigue (P = .011; APBI 43 vs WBI 49). The APBI group reported less pain (BCTOS) at EOT (WBI 2.29 vs APBI 1.97) but worse pain at 3 years (WBI 1.62 vs APBI 1.71). APBI patients reported greater convenience of care than with WBI and reported less symptom severity at EOT and 4 weeks later. Conclusion Cosmetic outcomes were similar for the APBI and WBI groups, with small statistically significant differences in other outcomes that varied over time. Differences in fatigue and other symptoms appeared to resolve by ≥6 months. APBI may be preferred by some patients, for whom extended treatment is burdensome. ClinicalTrials.gov NCT00103181.

Novel targeted therapies (small molecule inhibitors, antibody–drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton’s tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte–predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody–drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1–mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. Current management of classic HL involves initial treatment with chemotherapy alone or combined modality therapy followed by restaging with PET/CT to assess treatment response. Overall, the introduction of less toxic and more effective regimens has significantly advanced HL cure rates. This portion of the NCCN Guidelines focuses on the management of classic HL.

Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin’s lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.

508 Background: PBI is an alternative to WBI, with potentially greater therapy (tx) compliance, and better integration with chemotherapy (CTX). NSABP B-39/RTOG 0413 clinical outcome results from 2018 did not show equivalence of PBI to WBI in local tumor control; PBI was statistically inferior, but with clinically small differences. PBI may be an acceptable alternative to WBI for some women. Understanding cosmesis and quality of life (QOL) treatment outcomes is important. Methods: B-39/0413 included a prospective QOL substudy with PRO evaluation of breast cancer treatment outcomes (cosmesis, function, pain) and fatigue using BCTOS and SF-36 vitality scales. Secondary QOL parameters included treatment related symptoms, perceived convenience of care, and the BPI pain scale. The study sample was stratified by CTX or not, as CTX is given before WBI but after PBI. PRO assessments occurred before randomization, the last day of adjuvant tx [CTX or radiation], 4 wks later, and 6, 12, 24, and 36 mo later. Primary aims included comparisons of change in fatigue from baseline to end of tx and equivalency of change in cosmesis from baseline to 36 mo for PBI v WBI. Separate analyses were done for CTX and non-CTX pts, controlling for axillary dissection. Each comparison used α=0.0125. Planned sample size was 964. Results: From 3-23-05 to 5-27-09, 975 pts were enrolled in the PRO study; 950 had follow-up data. 504 did not receive CTX and 446 received CTX. In non-CTX pts, PBI had less fatigue (p=0.011) and did not meet criteria for cosmesis equivalence (97.5% CI, -0.02 to 0.22; ∆=0.20). In CTX pts, PBI had worse fatigue (p=0.011) and equivalent cosmesis to WBI (97.5% CI, -0.09 to 0.21; ∆=0.24). In both groups, PBI pts reported less pain at end of tx. In non-CTX pts, PBI had more pain at 36 mo but in CTX pts, there was no difference. Convenience of care and treatment related symptom outcomes will be presented. Conclusions: In non-CTX pts, PBI is more convenient with less fatigue and slightly poorer cosmesis at 36 mo. Cosmesis was equivalent at 36 mo in CTX pts. Support: U10CA180868, -180822, UG1CA189867. Clinical trial information: NCT00103181.